MXPA97006029A - Farmaco control system controlled by realimentac - Google Patents

Abstract

A feedback-controlled drug delivery system includes automated sampling of blood samples and analysis and dosing of the patient, automated sampling is carried out by direct analysis of the patient's blood, such as to measure their status. coagulation, a novel manifold includes an access path to the fluid inlet, an access path to the patient adapted to let out the fluid and to receive a blood sample from the patient, and a fluid path that connects the access path to the patient. fluid and the patient access path, a sample line is connected to the fluid path to provide the sample to an analyzer, in one aspect of this invention, the sample is forced through the sample line by isolating the pathway access to the patient, such as through a valve, and a fluid other than a drug is forced into the manifold, causing the blood to cross through the sample line, in another mode, a integrated samble includes an integrated peristaltic pump, a valve assembly, a selectively movable actuator and an integrated waste container, in one aspect, the peristaltic pump allows the retraction of the rollers away from the inner circumference of the pump, so that it reduces deformation of the tube of the peristaltic pump and allows sterilization

Description

DRUG CONTROL SYSTEM CONTROLLED BY FEEDBACK INFORMATION RELATED TO THE REQUEST This application is a continuation application in part of No. 08 / 386,916, filed on February 7, 1995, entitled "Feedback Controlled Drug Delivery System".

FIELD OF THE INVENTION This invention relates to the field of the drug delivery system controlled by real .. .. In other aspects, this invention relates to systems for the automatic obtaining of the sample or condition of the patient. Most particularly, this invention relates to the field of automatic oni + oreo schemes used in connection with variable dose drug delivery systems, especially for those for use with drug administration that otherwise requires a high dose. degree of monitoring by health care professionals.

BACKGROUND OF THE INVENTION A wide variety of drug delivery systems is known in the art, ranging from systems that rely entirely on health care professionals for dosing and administration decisions to highly automated systems that perform one or more functions such as these. as monitoring, analysis, dosing and dosing decisions. At the non-automated, simpler end of the spectrum, a drug delivery system may comprise a preset regimen performed at a preset infusion rate without feedback, just as a patient is given a prescribing dosing regimen. At a higher level of control, feedback systems are used in which the analysis of the current condition of the patient is used in a controlled manner by realization as input to the dosing analysis. These steps can be performed by the health care professional with or without the use of automation or computer tools. An example of a nomogram based, non-automated drug delivery system includes several heparma delivery systems now in widespread and widespread use, other similar systems use hirudma, hirulogo and other direct trope inhibitors. See, for example, Carr et al., "Glycoprotem Ilb / IIIa Bloc ade Inh bits Platelet-ediated Force Development and Reduces Gel Elastic Modulus", Thrornbosis and Haemostasis, DATE, pp 499-505. Heparma is a well-known anticoagulant used to prevent coagulation, such as during dialysis, trilbolytic therapy, acute non-stable angina, cardiac catheterization, coronary artery bypass surgery, fixation of fixative and PTCn, pulmonary embolism, deep thrombosis of the vein, treatment of transient ischemic attack and stroke. At certain intervals blood is drawn from the patient and analyzed for their ability to clot. Although heparin is generally considered as a relatively safe and effective drug, it can result in an increased risk of bleeding and a difficult outcome in selecting the ideal hepar- ma. There is a wide variation in the patient-patient response, both in the concentration of hepap that results from a given hepapine infusion rate and in the response of the patient to a given concentration of hepapn. Non-automated control is difficult and often inaccurate. Various available analysis units are available to analyze a small amount, for example a drop, of the patient's blood, to determine the state of blood coagulation. Based on this analysis, dosing decisions are made ad hoc or with the help of a nomogram. Heparin is then administered to the patient based on this decision. Several proposals have been made to automate the passage of the decision of the dosage in the hepapna supply. In Denme R. Mungall, and others, "O Prospective Randomized Co paper of the Accuracy of Cornputer-Assisted Versus GUSTO Nomograrn-directed Hepapn Therapy ", Climcal Phar acology S Therapeutics, May 1994, pp.591,596, a computer system used the activated partial time of t rornbopl st na (TPTO) measured over a preset interval as input to determine dosing decisions. r, and used a computer program of Bayes prognosis, assuming a non-linear non-linear model for heparin. The initial estimates of heparin requirements were based on prior knowledge of demographic characteristics, speci fi cally weight, sex and current conditions of smoking. Finally, in Kersha et al., "Cornputer-Ossited Dosing of Heparin, Management Uith to Ph rnacy-B sed Anticoagulation Service", Archives of Interna! Medicine, May 9, 1994, pp. 1005-1011, a computer-assisted heparin dosage was performed. We used TPTf measurements? as entry to the system. Finally, the specific work has taken place in an attempt to optimize the supply of drugs where scarce measurements are available. See, for example T.C. Jannet et al., "Simulation of Adaptive Control of Onticoagulation During Henodialysis," Biornedical Applications of Automatic Control, Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vol. 13, No. 5, 1991, pp. 2147- 2148 Several adaptive control systems have been proposed. These systems try to use data obtained historically and the response of the individual patient as input to the control system that determines the dosage of the drug. These adaptive control systems have a particular applicability to the dispensing systems of which scarce measurements are available. A system proposed by Jannet and others, previously, used a system based on a model with parameter estimation. Scattered measurements, at infrequent intervals or differently synchronized, are used in an attempt to estimate the appropriate supply of drug. At a higher level of integration, several automated drug dispensing systems are known in the art. Relatively simple systems that use non-invasive monitoring systems monitor a patient variable and provide dosing based on decisions by a control system in a controlled manner by feedback. For example, there are automated systems for monitoring blood pressure. Automated devices for blood pressure measurement are automatically activated, typically at pre-set intervals of time, which cause the increase in the pressure of the inflatable cuff in an automated system for measuring blood pressure and then detecting blood pressure. of the patient These systems generally try to maintain the patient at a pre-established level, such as a desired level of blood pressure. See, for example, Cosgrover Ir., And other US Patent. No. 4,280,494, or at a higher level of complexity attempt to allow natural variations a physiological variable of the patient, such as a circadian rhythm in blood pressure. See, for example, Frucht et al., "Cornputer-Assisted Blood Pressure Control by Cardiovascular Drugs - Problems in Developmg to Closed Loop Control System", Anasth Intesivther. Notfallmed. 21 (1986). Yet another non-invasive, non-invasive control system is the Genesa system from Gensia Inc. that monitors the patient's heart rate as a control input for a system that results in an assortment of an exercise simulator, such as arbutamma, in order to mimic the effects of aerobic exercise. In one application, such a system can be used to perform a cardiac stress test on patients, such as by varying the cardiac effort as a function of time. The control of certain physiological parameters requires the invasive monitoring of the patient, tai co or in systems that require direct analysis of the patient's blood. A VIA Medical system automatically extracts and analyzes the patient's blood. A dispensing device is connected to the patient's vein which is used with a dual fluid suction function, such as a physiological solution and exudation of the patient's blood. A pump is used to draw the patient's blood through the dispensing equipment. The analysis is carried out by extracting the blood through a closed circuit containing an input line with sensor. Sensors external to the patient measure several analytes in the blood. In a suggested operation, the blood drawn from the patient is cast to the patient. Still another blood analysis system is shown in Cusa, Patent of E.U.A. No. 5,134,079. A fluid sample collection system uses a patient sample, such as blood with an immiscible fluid, such as air, and a wash fluid, such as saline, to segment portions of the patient's sample and to transport them to a patient. analyzer. The blood and saline are connected by a fluid path, which in combination forms a transfer tube to pass the blood and saline solution alternately to the analyzer. From a fluid mechanics point of view, the patient sample and the immiscible fluid are brought in from the inlet access ways that form a Y connection with the fluid path to the analyzer. A third entry port forms a T-connection with the fluid path and provides the input for the immiscible fluid to the fluid path. A downstream pump causes movement through the tube of the fluid path. A detector is placed in downward flow of the pump but in ascending flow of the output path to the analyzer. In each of the described operation modes, blood segmentation is required. No measure is taken for the return of the blood obtained to the patient that is not used in the analysis.

Various gas measurement systems in the blood are known in the art, some of which are invasive and some of which are invasive, a similar system is developed by FOxS Systems which comprises an interal-gas system in the blood that they measure the pH, PCO2, O2 and temperature on a continuous basis. The system uses optical fluorescent sensors optimized for each analyte of interest. A Diametpcs system performs gas analysis in the blood using a small cartridge inserted in front of a * IRMA. After the calibration step, blood pressure is injected into the cartridge that performs the analysis. The B? OstatortM system from Miles Laboratories is a dispensing system for controlling drugs by invasive realization. A line connects the patient in a closed circuit that serves to provide the fluid assortment such as a saline solution, to the patient as well as to the sample blood of the patient. The sample blood is then analyzed to determine the glucose concentration, which is used to calculate an insulin infusion rate to control the level of glucose in the blood. Although much progress has been made in the general field of automated, real-controlled drug assortment, deficiencies remain for certain applications. Current systems for therapeutic dosing often consume a lot of time, requiring the direct intervention of a health care professional. The automatic analysis is often difficult or impossible and requires considerable expertise and training on the part of the health care professional. In such circumstances, it is difficult to perform such therapeutic dosing in an environment other than a hospital, such as home health care. In addition, given the multiple step and the full nature of the measurement, analysis and dosing steps, errors can occur in any of these steps and cause the cumulative effect, causing risk to the patient. Furthermore, being often requires a high degree of role, especially for the administration of anticoagulants, where the therapy has a narrow LCO therapeutic index (ie, a too low dose will result in diminished efficacy such as reappearance of deep vein thrombosis (TPV) and too high a dose will result in side effects, such as bleeding and oropathic access). Current practice requires a multi-step operation, each step incurring the possibility of error. Generally, these steps are as follows: the patient is hooked to the IV unit of heparin, a bolus of hepapna is administered, a sample is withdrawn and sent to the laboratory, the laboratory analyzes the sample as to the value of the TPTA, the nurse receives the results, from a possible delay of up to more than one hour, the dose of heparin is determined, based on the order of the doctor or using a nomogram, pump IV is adjusted with the new proportion of heparin and the following is determined Sample time. Cumulative errors may occur in the suboptimal sucking portions. Despite numerous attempts to provide a more automated and reliable system for the drug assortment, no satisfactory solution has been proposed for systems that require invasive monitoring of the patient's blood and subsequent control of anticoagulant effects.

BRIEF DESCRIPTION OF THE IVENTION The invention comprises a realistically controlled drug delivery system particularly adapted to perform automated blood analysis, calculate the optimal dose and control a drug delivery system to adrnimstar the dose to the patient. The methods and apparatus for obtaining blood, the control system and the drug mixture connected to each other include all novel aspects of this invention. In the preferred embodiment, this invention is used with a delivery controlled drug delivery system that requires the removal and automated analysis of the patient's blood., such as with regard to its state of cuagulación, and the determination of the optimal dose to be supplied. That optimal quantity is calculated for a system that has frequent measurements and then the drug assortment is determined, such as an an icoagunte. From one point of view the system provides one or more sources of drug to the patient in a controlled manner, such as the assortment through a pumping system. The control of the pumps is carried out by a control system that uses the measured variable of the patient as input information. Structurally, one or more drug sources and, optionally, a source of fluid, for example saline, are operatively connected to a pump or pumps to control the flow rates to the patient. A novel multiple is connected to the patient, the saline solution and the analyzer. The manifold includes an inlet port adapted to receive a fluid, for example saline or drug, a patient access port adapted to deliver fluid to the patient and receive the patient's blood, connecting a blood line to the patient. access route of the saline solution and the patient access route, and a sample line connected to the fluid path, the sample line having an inlet connected to the fluid path and an outlet directed towards the analyzer. A force path of the pump is connected to the fluid path at a point between the access route of the saline solution and the sample line, and a pump force on the fluid path is adapted to privet. Optionally, a position of the detector between the 1 A pump force access path and the access to the analyzer serves to detect the inter-facial zone between the blood and a more transparent fluid, such as a saline solution. In one embodiment, an integrated assembly is provided that L2 It includes one or more of the following: an integrated peristaltic pump (also known as pepbornba) with retractable rotors, valves and an integrated waste unit. Preferably, the peristaltic pump includes rollers that are movable to and from the peribomba tube to reduce the deformation of the tube and to allow easy sterilization. Such an integrated unit, preferably disposable, provides ease of operation and intergration. In operation, the manifold may be operated in order to draw a sample of the patient's blood from a portion of the specific or defined volume of blood displaced from the anterior edge of the defined volume. In the preferred mode of operation, the assortment of saline solution to the patient occurs in normal operation through the fluid path to the manifold. To obtain a blood sample, the source of the saline solution is disconnected from the fluid path, such as by operation of a bar valve, followed by the activation of the pumping force, thus causing the saline solution in the path of fluid is sucked into the pumping force. This flow of the fluid at the same time causes the patient's blood to be extracted from the patient through the patient's access route to the manifold and through the fluid pathway. Once the blood is sucked through the fluid path to a position beyond the intersection of the pathway to the analyzer, as is preferably determined by the detector, the defined volume of blood will present a non-anterior edge in the blood. opening of the analyzer access. The blood from the non-anterior edge of the defined volume can then be supplied to the analyzer. In the preferred embodiment, the blood is drawn to the analyzer through the analyzer path, preferably closing a valve to the patient's access path, urging the fluid, eg, saline, to the access port of the manifold , the resulting action being that the non-anterior edge of the defined volume of blood is forced towards the analyzer. Alternatively, a pumping force can suck blood into the analyzer. In another aspect of this invention, a computer corvoured system uses defined sample data, often scattered, as input to the control system. Optionally, the dosing history of the patient and / or the response can be used in the control system. Expert systems can be used, especially for drugs that are difficult to administer. The control system outputs the dosing information to the drug delivery device. Analysis systems that previously require individual test cartridges for a single test are combined in a multiple unit arrangement. In one embodiment, a carousel comprising multiple individual test units allows the rotary movement of the test units below the source supply location. In another embodiment, the multiple individual test units are joined in a stacking arrangement, with the new units being used on or off the stack as needed. A pulse unit can insert 1 A individual test unit into the system, with an optional coupler key that is provided to remove the test unit from the system after analysis. In yet another aspect of the invention, an entanglement system for coupling and interlocking-cooperatively and positively a drug source, for example heparin, is used at an entrance to the remainder of the drug delivery system. Optionally, the zone includes a miter system, such that if an unauthorized drug source is attempted to be used with the system, the system is disabled. In this way, a defined source of hypapna can be used to minimize the variability of hyparine and patient variability. In still another aspect of this invention, the system may include an inflatable cuff attached to the patient that is inflated prior to obtaining the blood sample from the patient. patient. Preferably, the inflatable cuff is automatically inflated under the control of the system. It facilitates the removal of blood from the patient. In yet another aspect of this invention, the system may include a motion detector in order to disable or otherwise limit the analysis of the system during the movement of the system. Accordingly, it is an object of this invention to provide a automated, feedback-controlled drug delivery system capable of being used with drugs that require a high degree of patient monitoring. It is still an additional objective of this invention to provide an improved apparatus and method for the automatic collection of blood samples for use in an external circulation circuit and analyzer. It is an object of this invention to provide an improved device for use in the field of intensive drug and home care assortment. It is still another object of this invention to provide an automated drug titration based on an automated measurement of a patient parameter. It is still another object of this invention to provide a useful system with antiplaquet aggregation tests. It is still another object of this invention to provide an improved system for the optimized assortment of a drug to maximize the therapeutic benefit. In yet another aspect of this invention, a novel disposition of test cartridges for the analyzer is used.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a perspective view of the drug delivery system controlled by feedback in a modality. Figure 2 shows a schematic diagram of the fluid system in one embodiment. Figure 3 is an on-plan view of a switch useful for alternately supplying blood to the analyzer or to a second inlet. Figure 4 shows a perspective view of an integrated manifold. Figure 5 shows an alternate system of fluids. Figure 6A shows an end view of a stacked multiplexed test unit system. Figure 6B shows a perspective view of an individual test disk for use in a rnutlipies test unit. Figure 7 shows a perspective view of a flat carousel arrangement for multiple locations of test sites. Figure 8A shows a perspective view of a carousel of multiple test site locations. Figure 8B shows an end view of the structure of Figure 8A. Figure 9A shows a sliding tray arrangement in top view. Figure 9B shows a sliding tray arrangement in side view. Figure 10 shows a perspective view of a line of test cartridges and bar code. Figure HA shows an alternative arrangement with a sliding tray in top view. Figure 11 B shows an alternative arrangement of sliding tray in side view. Figure 12A shows an integrated assembly in top view. Figure 12B shows a detail of the closing blood-sorting opening of Figure 12A. Figure 13 shows a plan view of the roller mechanism of a peristatic pump. Figure 14 shows a plan view of a roller mechanism and assembly.

DETAILED DESCRIPTION OF THE INVENTION Figure 1 shows a perspective view of the components of this invention in a preferred embodiment. A patient 10 is coupled to the system through a multiple lumen catheter (not shown) that gives access to a patient's vein to the access point 12. The preferred catheter is one manufactured by Arrow International, Inc. called the Arro? Twin CathR. One or more sources of drug 16 and source of fluid 18, such as saline, are connected to a pump system 20. The pump system is preferably able to control the flow of fluid from drug source 16 and the source of fluid. fluid 18. The drug assortment to patient 10 takes place through the drug spout 22 as measured and monitored by the pump 20. The spout 22 is connected to a lumen of the multiple lumen catheter. The outlet of the fluid source 18 as measured and pumped by the pump 20 is expelled through the fluid spout 26 to the analysis and control system 28. A tube 30 provides connection between the analysis and control system 28 and patient 10, preferably through a different lumen of the multiple lumen catheter. The tube 30 preferably provides bidirectional flow of the fluid, providing transfer of the fluid source 18 to the patient 10 of the fluid, for example saline, and at alternate times, transfer of the patient sample, such as blood from patient 10 to the delivery system. Analysis and control 28. The analysis and control system 18 provides control signals to the pump 20 through the connection 32. The pump 20 and the analysis and control system 28 can be conveniently arranged on a conventional support 34. The system of analysis and control 28 is shown as a single integrated unit, although it may be formed into one or more components as desired. The analysis and control system 28 as shown is adapted to receive a multiple test unit 36 as inserted into a receiving slot 38. A directional arrow shows the insertion action of the multiple test unit 36 into the receiving slot 38 In one aspect of this invention, an interlacing system is used to provide an inter-facial zone between the drug source 16 and the pump 20. The interlacing system 40 is adapted to provide limited interconnection between authorized drug sources 16 and the rest of the system. The interlacing system 40 may include interlacing mechanical components and / or electrical interlacing components. Figure 2 shows a schematic version of a fluid system according to this invention. A drug source 50 and a fluid source 52 are connected through the fluid pathways to the EV 54 pump system. Preferably the IV pump system 54 is a multi-channel IV pumping system adapted to regulate the flow of the pumps. several sources, such as the multiple potential drug sources 50 and the fluid sources 52. The arm of the patient 56 is in fluid contact with the IV pump system 54 for the drug assortment of the drug source 50. A multiple 58 is shown included within the dotted lines. The manifold includes a fluid access path 62 adapted to receive the output from the fluid source 52 as regulated by the pump system IV 54. A patient access path 64 provides connection to the patient's arm 56 through a tube comprising a fluid connection. The patient access path 64 alternately provides fluid exit that starts at the source of fluids 52 to the patient's arm 56, and at alternate times, receives blood from the patient's arm 56 as input to the manifold 58. The access path of fluid 62 is connected to the patient access path 64 through a fluid path 66. A sample line 68 is connected to fluid path 66. Preferably, the sample line 68 forms a T-intersection with the fluid track 66 at intersection node 70. Sample line 68 provides transport of fluid materials from fluid path 66 to an analysis system. Optionally, the sample line 68 terminates in an inter-facial zone access path 72 of the analyzer. Optionally, a waste access path 74 can be provided as an input to the manifold 58 adapted to receive the waste output of the analyzer 76. The transfer of fluids through the manifold 58 is controlled by the operation of the IV pump system 54 and the additional pumping forces. Such additional pumping forces may be provided by a pump 78 or, alternatively or additionally thereto, a source of vacuum 80. In this mode, the pumping force is supplied in order to selectively receive materials from the access path No. 64 and the fluid path 66. The pumping force is supplied to the fluid path 66 through a pump connection 82. The pump connection 82 preferably forms a T-connection to the fluid path 66. The Fluid flow within the manifold is also controlled by the operation of valves. An upflow isolation valve 84 is preferably disposed on the fluid path within the manifold 58 in downflows from the fluid access path 62. A patient closure valve is preferably located in the fluid path 66 in upflow of the patient path 64 and in downflow of the sample line 68. An access valve 88 of the analyzer is preferably disposed adjacent the intersection node 60, preferably on the sample line 68. A waste valve 90 is interposes between the waste access path 64 and the source of the pumping force. A pumping force valve 92 is disposed between the pumping force and the fluid path 66, optionally with a certain section of the pumping connection 82 disposed between the pumping force valve 92 and the fluid path 66. In one aspect of this invention, a detector 94 is preferably positioned to determine the position of the fluid or blood within the manifold 58. In the preferred embodiment, the detector 94 is placed adjacent to the fluid path 66 between the isolation valve 84 in updraft and the intersection node 70. Very particularly, if a pumping force is supplied directly to the fluid path 66. As shown, the detector 94 is preferably positioned between the intersection of the pump connection 82 and the intersection node 70. Any form of detector 94 consistent with the objectives of this invention can be used. The preferred detector uses optical changes in the content of fluid path 66 to detect a change. For example, an optical detector 94 can detect the inter-facial area of blood / saline when that interface zone! is adjacent to the detector 94. An ultrasonic detector can be used to detect the presence of fluid in line 66. In operation, the system can be operated where the patient receives fluid, such as saline, from the fluid source 52. In in that case, the fluid is received in the fluid access path 62 and is transferred through the fluid path 66 and the exit to the patient access path 64 with the valves 84 and 86 open. Ordily, this can occur simultaneously with the drug infusion from the drug source 50. To carry out this measurement the drug flow is preferably terminated, in order to allow an accurate reading of the patient's condition. To obtain * a blood sample from the patient, the isolation valve 84 is closed in upflow and fluid force pumping force 66 is applied. In the described mode, the pump 78 provides pumping force on a connecting line pump 82 through the pump force valve 92 now open. This causes the sample to be sucked through the patient access path 64 beyond the patient closure valve 86 now open. The pump 78 provides the saline solution removed to the waste container 80. The blood is sucked at least to the intersection node 70 and preferably to the detector 94. Once sufficient blood has been sucked out, the blood is then taken from the blood node. intersection 70 through the sample line 68 to the analyzer 76. In one embodiment, the blood is drawn through the sample line 68 by closing the patient closure valve 86, opening the analyzer access valve B8, closing the pumping force valve 92 and opening the upstream isolation valve 84. This combination allows the material of the fluid force 52 to be pumped by the pumping system IV 54 through the upstream pressure of the flow path. fluids 66 to cause the flow of the defined volume of blood upwardly and through the sample lines 68. Advantageously, if the defined volume of blood has a leading edge disposed in ascending flow of the intersection node 70, the blood in the sample line 68 becomes the non-anterior edge of the defined volume of blood in the fluid path 66. Alternatively, the blood can be sucked from the intersection node 70 by a pumping force applied to the sample line 68 directed towards the intermediate superscope access path of the analyzer 72. In the embodiment shown, the analyzer 76 receives a blood sample from the nfafacial zone access path of the analyzer 72. A sample nozzle 96 serves to supply the blood to the test unit 98. Optionally, the sample nozzle 96 can be placed in juxtaposition to the waste access path 74 to discard the leading edge of the defined volume of blood traveling through the lines sample 68. Sample nozzle 66 can then deliver a clean blood sample to test unit 98. After the blood is supplied to test unit 98, the sample iple 58 can be filled with saline, also serving to clean the sample nozzle 96. Disposal of this material of the sample nozzle 96 is through the waste access path 74. The remaining blood of the patient in the manifold and the connection of the patient access path 64 to the arm of the patient 56 can be returned to the patient. Figure 3 shows a plan view of a valve arrangement that allows the selective assortment of a blood sample to an analyzer or the continuation of a blood circuit. A rotary valve 200 receives a blood sample as inlet of track 202. In an orientation of the rotation valve 200, the track 202 is connected to an output path 204. When the rotary valve 200 is rotated 90 ° (in the counterclockwise direction in Figure 3) the rotary valve 200 provides connection of the track 202 to the analyzer (not shown). By the rotation of the valve 200, the blood can be directed to the analyzer (such as an aPPT cartridge) or to a waste cartridge by a simple rotation. Figure 4 shows a perspective view of an integral multiple assembly. The manifold 100 is preferably formed of plastic, such as polycarbonate, ABS, SAN, Styrolite ™ and? other suitable material that can be used, including sterilisable with gamma rays, electron beam and ethylene oxide. The tubing is preferably made of a material that does not promote heparin agglutination (eg, a Teflon tube, or PVC or polyurethane tube with covalently bound heparin). The size of the tubing is selected to prevent hernodialysis of the blood. A patient access path 102 is connected to a fluid path 104 that is coupled to an access path to the fluid 106. A detector 100 is optionally located in the fluid path 104. A sample line 110 is coupled to the pathway. of fluid 104, terminating in an interface zone access path of analyzer 112. A pump connection 114 connects to fluid path 104. A pumping force is supplied to vacuum region 116. The vacuum force in the vacuum region 116 may be provided by any known method consistent with this invention including, but not limited to, the use of a peristaltic pump, a vacutainer or a linear pump or a vacuum pump such as that which is formed through a syringe that has a linear force applied to the syringe. Optionally, if the vacuum force is generated by a vacutainer, a pin 118 may be used to interconnect the vacutainer. The pin 118 can also function as a distribution connection. An isolation valve 120 upstream, a patient closing valve 122, an access valve to the analyzer 124, a distribution valve 126 and a pump force valve 128 are used as described in relation to the named valves of the same way in figure 2. A vacuum valve 130 optionally provides for the selective interconnection of the vacuum source with the manifold 100. The heparin assortment controlled by feedback occurs in a "data poor" environment. Measurements of the patient's condition can not be obtained on a frequent basis. In the preferred embodiment, the infusion rate calculated by the control algorithm is based on a pharmacodynamic (PD) model of the hepapna response. Since there is great variability in patients with respect to heparin, there are a number of parameters in the PD model that describe the individual responses. Based on measurements of the patient's response, the parameters of the model can be adjusted. Since the measurements are scarce and subject to certain uncertainty, the estimates of the patient's parameters will have a certain confidence interval that will affect the expected precision of the control. The information used includes values of the parameters of the population, including values of variance and values of accuracy of the measurement. The programming of the samples can be optimized, although the system imposes certain limits on the frequency of the measurement (such as the cost and the limited number of cartridges). The control system optionally determines when the additional information of a new measurement would be more beneficial based on the response observed in the patient, the history of the infusion adjustment, the desired precision in the control level and the confidence of the parameters of the model. Figure 5 shows a schematic view of an alternative arrangement of the fluids to those shown in Figures 2 and 3. The drug source 140 is controllably connected to the patient's arm 142 through the pump 144, as described above. The fluid source 146 is selectively connected to the patient's arm 142 through the pump 148. The path of the assortment tube 150 is connected to the patient's arm 142, preferably through a Y-connector 152. The Y-connector 152 is additionally connected to the sample path 154. The sample path 154 is operatively connected to the sampling system 156. A vacuum force is supplied to the sample path 154, such as by operation of a pump. Peristaltic 158. The arrangement is by any desired means, such as through a vacutamer 160. Optionally, a detector 162 may be used, in the preferred embodiment the detector 162 as shown, comprising an optical window that is used in conjunction with a detector. optical. A valve of the sample system 164 serves to isolate the sample path 154 from the sample return system 156. A pump valve 166 serves to isolate the pumping force, such as that generated by the peristaltic pump 158 from the system. of sampling 156.

During the operation, the sample takes place by terminating the drug assortment and moving the fluid from the fluid source 146 through the pump 148, through the Y connector 152 and through the sensing pathway 154. Optionally, a control valve or an electronically controlled valve is used. The flow of the fluid is facilitated by the pumping force supplied by the pump 158, the valves 164 and 166 being open. The pump 148 is then turned off, resulting in the removal of blood from the patient. Optionally, a control valve 168 is used to control the flow of fluid and blood. The blood is then pumped through the sample port 154. When the blood passes the detector 162, the system can use that time and the pump speed to calculate the pumping time necessary to cause the assortment of blood in the system. Sampling System 156. After the sample has been dispensed to the sampling system 156, the flow of saline through the pump 148 can be used to provide a source of jet wash of the fluid from the sample. source 146 through sample path 154. After the sample is supplied to the sampling system 156, it can be analyzed and the data used in the feedback controlled control system. Figure 6A shows a side view of stacked multiple test units. Each test unit 170 comprises a test site 172 on which the biological material to be analyzed is provided. This test can include any of the desired tests, such as the monitoring of the coagulation status, the TPT test such as that prepared by Boeh mger Mannheim Diagnostics, Cardiovascular Diagnostics Inc. or International Technidyne Corporation. Alternative tests include activated coagulation time (ACT), factor X or Xa, partial-time thromboplasty tests, whole-blood clotting time tests, or any general hepap-a test. Optionally, the test unit 170 may include a keyhole 174 to facilitate orientation of the unit 170 during loading. Optionally, nesting depressions 176 may be provided to promote stacking of the test disks 170. An opening for the blood drop 178 may be provided to access the test site 172. FIG. 7 shows a perspective view of an arrangement planar carousel comprising multiple test units. A carousel 180 includes multiple test units 182 (five being shown in Figure 7). The individual test units 182 are arranged symmetrically about an axis of rotation for the carousel 180. The individual test units 182 are mounted on a stage 184 that allows rotation thereof with respect to the housing 186. Figures 8A and 8B show views of an alternative arrangement for providing multiple test units for a detector. The test units 190 are fixed to a housing 192 having sequential faces at the upper end of a reading unit 194. In the embodiment shown, the cartridge 192 includes five faces on which the test units 190 can be disposed. The cartridge 192 has a rotation ee that allows sequential apposition of a test unit 190 with the upper end-of the reading unit 194. An arrow indicates the rotational movement of the cartridge 192 with respect to the upper end of the reading unit 194. Optionally, it can a heater 196 is used to facilitate the test procedure as performed by the test unit 190. Figures 9A and 9B show a top view and a side view of a multi-test cartridge enclosure. A cartridge 210 serves to contain individual multiple test plates 212. The cartridge 210 serves to contain the microcircuits 212 in a stacked arrangement. An arm 214 causes the displacement of the nicrocircuit 212 of the cartridge 210 to a test stage 216. The microcircuit 212 in the test stage 216 receives a drop of blood on which the analysis is carried out. After the test has finished, the microcircuit 212 is reinserted into the cartridge 210. Preferably, the cartridge 210 is formed with two chambers, an upper chamber 218 containing the unused microcircuits 212 and a lower chamber 220 containing the used microcircuits 212. The used microcircuit 212 is removes from the test stage 216 by optionally lowering the test stage 216 relative to the cartridge 210, with optional lateral force applied to the microcircuit 212 which causes the microcirculation used to be inserted into the lower chamber 220. Figure 10 shows a perspective view of a multiple test cartridge system, in which the individual multiple test sites 230 are disposed laterally adjacent to each other. Each individual test site 230 may be mounted on a substrate 232, or formed only adjacent to each other, resulting in a unitary structure. Optionally, a bar code 234 is provided on the system of multiple test cartridges. In one embodiment, bar code 234 may contain information indicating the specific activity of the tests. For example, if TPT tests are used in that system, the tests tend to vary from manufacturer to manufacturer, and are even subject to different results being reported by different operators. The automated system of this invention allows encoding the information (such as through the bar code) that tells the system the degree to which the test results must be corrected in order to provide a standardized result. In one aspect of this invention, the system can be provided with test units that allow to measure both the coagulation status (as well as through the use of a TPT test) and the prothrombin time (PT). Such combinations are particularly useful when the patient is switching from an IV heparin to warfarin administration, during which time TPT measurements are affected by the presence of warfapna. At this moment he faces the difficulty to title the hepapna. 01 provide separate measurements of TP and TPT, the system can be corrected for the presence of warfap a and administer convenient amounts of heparin, and determine the optimal dose of warfapna. Figures HA and B show a top view and a side view, respectively, of an alternative arrangement for a multi-test cartridge enclosure. One or more nicrocircuit 240 may be arranged in a stacked configuration. An icrocircuit 240 at a time is inserted into the test unit 242 on the test stage 244. In this mode, e! arm 246 moves the nicrocircuit 240 in useful position on the test stage 244 of the test unit 242. After the test has concluded, the arm 246 retracts, removing the now used microcircuit 240 from the test stage 244 In the preferred embodiment, the microcircuit 240 used is disposed in a receptacle 256 by gravity. In one embodiment, a key system provides a lock coupling between the arm 246 and the microcircuit 240. This allows the used mini-circuit 240 to be removed from the test stage 244. The arm 246 includes a key 248 at the terminal end of the arm 246. The key 248 serves to engage the latch 250 to provide retraction force for the used microcircuit 240.

In the preferred embodiment, movable latches 252 are adapted to mate with the cavities 254 in the key 250. Preferably, in FIG. 252 they flex, such as toward the center line of the arm 246 to positively close with the key 250. After the machine 240 has been used and removed from the test stage 244, the used tool 240 drops to the receptacle 256 as the key 248 is separated from the safe 250. Optionally, a calibration circuit or Quality control 258 can be inserted into the test unit 242 for calibration or quality control purposes. In one embodiment, the microcircuit 258 can be moved relative to the test unit 242 and then inserted into the test stage 216. Said action ensures continuous calibration or proper operation of the test unit 242. FIGS. 12A and 12B show, respectively, the top and detailed views of an integrated assembly for the receiver, the sequential assortment of blood drops, and the storage of waste material. In the preferred embodiment, the assembly 260 includes an external housing 262 that includes an opening 264 adapted to supply blood to a unit of analysis (see, for example, microcirculation 240 in FIG. HA). The assembly 260 includes an inlet 266 for receiving blood or other fluid, which is connected through an inlet tube 268 to a first inlet valve 270. An assortment tube 274 is connected to an assortment unit 276 which will be described later in detail. The assortment unit 276 is operatively connected to the pump 278, such as by a pump inlet 280. The outlet of the pump 278 is connected via a pump outlet 282 to a receptacle 284 through an inlet 286. The connection of the pump outlet 282 is disposed partly under the inlet tube 268 and is hidden in Figure 12A. The assortment unit 276 is designed to selectively deliver a measured amount of blood or other material. In the preferred embodiment, an actuator 290 moves relative to the housing 262 to cause the sleeve 292 to move the pivot arm 294. The pivot point 296 falls on the pivot arm 294, causing the arm 298 to move away from the pivot arm 294. assortment unit 276. Optionally, spring 300 provides a restoring force that causes arm 298 to be sealed with assortment unit 276. Arm 298 terminates in a closure member 302, causing the assortment unit to be sealed. The assortment unit 276 is shown in detailed cross section in Figure 12B. Preferably, the assortment tube 274 and the pump inlet tube 280 are connected to an assortment unit 276. In one embodiment, the assortment unit 276 includes a switch 304 adapted to engage the closure 302 sealingly. The switch 304 it is formed with an opening 306 that allows the flow of blood or other fluid from the assortment unit 276. When blood or other materials are going to be filled through the opening of the housing 254, the closure 302 moves away from the unit. assortment 276. Preferably, the closure 302 may be disposed in the flow path between the assortment unit 276 and the opening of the housing 264 to allow the washing of the arm 298, particularly the closure 302. In the preferred embodiment, the pump 278 consists of of a pepstalti pump of the roller type. In the preferred embodiment, the pump 278 is integrated with the assembly 260. In one embodiment, a pulse rotor is coupled to the hub 300 to drive the perineal pump. Figure 13 shows a preferred embodiment of the pump 278 in detailed plant view. A tube 310 is provided adjacent to the inner circumference 312 of the housing. The tubing 310 is actually connected to an inlet and an outlet, such as the pump inlet 280 and the pump outlet 282, respectively. The rollers 314 exert pressure against the tube 3.10, and when they are driven rotationally around the hub 308, they cause the fluid in the tube 310 to move. In one aspect of this invention, the rollers 314 are adapted to approach and move away from the hub 308. The rollers 314 can be moved from their fully extended operational position adjacent the tube 310, such as before using the pump 378. This is advantageous in that the tubing 310 can then be sterilized with ethylene oxide, preventing deformation of the tube. A structure that allows to achieve the radial movement of the rollers 314 is through first arms rigidly connected to the impulse hub 308 and arranged in a radial direction. Conventionally, three rolls 314 are used, although the number may vary. Each of the preferably three first arms 316 is connected to second arms 318 or are rotatable about the axis 320. The cam 322 selectively moves the second arms 318, so that it causes the roller 314 to move closer and away from the inner circumference 312 of the accommodation. Figure 14 shows a plan view of an alternative arrangement that allows to adjoin a peristaltic pump with the assembly. A housing 320 includes within it a tube 322 that is adapted to carry a fluid, such as blood. A peristaltic pump rotor 3 4 includes rollers 326 and a hub 328. The rotor 324 is adapted to move towards the housing 320, so as to conform to an indentation 330 in the housing 320. During operation, the rotor 324, rollers 326 and hub 328 move in space 330, so as to exert pressure on tube 322 to achieve pumping action through rotation of hub 328. Although the invention has been described with respect to specific preferred embodiments , many variations and modifications may become apparent to those skilled in the art. Therefore, it is intended that the appended claims be interpreted as broadly as possible in view of the prior art including such variations and modifications.

Claims (54)

NOVELTY OF THE INVENTION CLAIMS

1. - An integrated assembly for the selective assortment of blood to a unit of analysis comprising: an inlet adapted to receive fluid; a way that connects the entrance to an opening, the opening being oriented to supply blood to the analysis unit; a selectively sealable opening for supplying a drop of blood; and a pump that has an inlet and an outlet, the inlet being connected to the track.

2. The integrated assembly of claim 1, wherein the fluid adapted to be received at the inlet is a biological fluid.

3. The integrated assembly of claim 2, wherein the biological fluid adapted to be received in the blood stream.

4. The integrated assembly of claim 1, wherein the fluid adapted to be received at the inlet is saline solution.

5. The integrated assembly of claim 1, wherein the selectively sealable opening includes a movable arm, the arm including a closure adapted to be selectively hermetically sealed to the opening.

6. The integrated assembly of claim 5, wherein the arm is connected to a pivot arm.

7. - The integrated assembly of claim 6, wherein the arm connected to the pivot arm is adapted to rotate, thus resulting in the movement of the closure away from the opening.

8. The integrated assembly of claim 1, wherein the pump is a peristaltic pump.

9. The integrated assembly of claim 8, wherein the peristaltic pump includes three rollers.

10. The integrated assembly of claim 8, wherein the peristaltic pump includes retractable rollers.

11. The integrated assembly of claim 10, wherein the retractable rollers are capable of moving away from the tube of the peristaltic pump.

12. The integrated assembly of claim 8, wherein the peristaltic pump is adapted to a gap in the assembly.

13. The integrated assembly of claim 1, further including a valve arranged in the way between the entrance and the opening.

14. The integrated assembly of claim 1, also including a storage receptacle connected to the outlet of the pump.

15. The integrated assembly of claim 14, further including a valve disposed between the peristaltic pump and the storage receptacle.

16. The integrated assembly of claim 15, further including a detector for determining the position of the biological fluid in the assembly.

17. The integrated assembly of claim 16, wherein the detector is an optical detector.

18. A pepstatic pump adapted to pump-fluid through a tube, the tube being arranged adjacent to the inner circumference of the pump, the pump including rollers connected to a pulse mechanism, which in the pump configuration makes the pump The roller is pressed against the tube, so that by applying a driving force to the driving arms, the rollers force the fluid through the tube, the improvement comprising the selective retraction of the rollers from the tube.

19. The peristaltic pump of claim 18, wherein the retractable rollers are retracted by rotating a cam.

20. The peristaltic pump of claim 19, wherein the cam exerts pressure on a second arm that holds the roller, the second arm being rotatably connected to a pulse mechanism.

21. The peristaltic pump of claim 18, wherein the pulse mechanism includes a first arm connected to a pulse hub.

22. A feedback-controlled drug delivery system, in which the automated blood sampling of the patient is extracted and analyzed as it enters the control system by feedback, the improvement comprising a movement detector included in the system to disable the measurement of the patient's blood while the movement is detected.

23.- A manifold that is used in relation to the extraction of a sample from a patient, the multiple interconnecting the patient, a source of fluid and an analyzer, the manifold comprising: a pathway to the fluid adapted to receive the Fluid source fluid; a patient access path adapted to the output fluid and to receive the patient sample; a fluid path that connects the access route to the fluid and the access route to the patient; a sample line connected to the fluid path, the sample line having an inlet connected to the fluid path and an outlet directed to the analyzer; and a pump force path connected to the fluid path at a point between the fluid access path and the sample line, operatively connected to provide a pumping force on the fluid path.

24. The multiple of claim 23, further including a detector for detecting the position of the sample, from the patient, within the multiple.

25. The manifold of claim 24, wherein the detector is positioned to determine the position of the sample within the fluid path.

26. The manifold of claim 25, wherein the detector is located to determine the position of the sample within the fluid path at a point between the pumping force path and the sample line.

27. The multiple of claim 24, wherein the detector is an optical-detector.

28. The manifold of claim 24, wherein the detector is an ultrasonic detector.

29. The manifold of claim 23, further including v valves that isolate the entry or exit of the manifold.

30. The multiple of claim 29, also including a valve in the access route to the patient.

31. The manifold of claim 29, further including a valve of the fluid access path.

32. The manifold of claim 29, further including a valve of the sample line.

33. The multiple of claim 23, wherein the fluid source comprises saline solution.

34. The multiple of claim 23, wherein the sample of a patient comprises blood.

35.- The manifold of claim 23, wherein the manifold is formed of plastic.

36. The multiple of claim 23, wherein a rotary valve is connected to the sample line and provides selective coupling of the patient sample to the analyzer.

37.- A drug delivery system controlled by r-eal? Nnentac? On to supply a drug and a fluid other than a drug to a patient, the system comprising: an input to receive fluid other than a drug; an infusion pump connected to the inlet to receive the fluid other than a drug to control the fluid assortment other than a drug as regulated by the pump; An analyzer adapted to receive a sample of the patient; and an interconnection between the fluid pump other than a drug, the patient and the analyzer, the interconnection comprising: an input adapted to receive fluid other than a drug; an outlet connected to the patient to let fluid other than a drug flow out to the patient; a fluid path formed between the entrance and the exit; and a connection between the fluid path and the analyzer.

38.- The medication delivery system controlled by realization of claim 37, wherein the output connected to the patient is also adapted to receive a sample of the patient at the entrance.

39.- The feedback controlled drug delivery system of claim 37, wherein the patient sample is blood.

40.- The dispensing system of drug controlled by realinentation of claim 37, further including a drug entry operatively connected to the patient ba or control of the system.

41.- The drug delivery system controlled by r-ealirnentacion of claim 37, wherein the drug is hepapna.

42.- The feedback controlled drug delivery system of claim 37, wherein the drug is selected from the group consisting of: hirudin, Hirulog and direct thrombin inhibitors.

43.- The feed pump system controlled by feedback of claim 37, wherein the drug is an Ilh / IIIa antagonist.

44. The delivery controlled drug delivery system of claim 43, wherein the analyzer is a platelet aggregation test or Ilb / TIIa test.

45.- The delivery-controlled drug delivery system of claim 37, further including a muting adapted to positively connect between a predefined drug source and the rest of the system.

46.- A multiple test cartridge that is used to perform the automated test of a patient, the cartridge comprising:? A carrousel cartridge having a central axis of rotation and including positions of individual multiple test sites, positions of the test sites being located substantially equidistantly from the axis of central rotation of the cartridge.

47.- The multiple test cartridge of claim 46, further including means for driving the carousel in a rotatable manner around its rotation access.

48. The multiple test cartridge of claim 46, wherein the test sample measures TPT, ACT Factor Xa, whole blood coagulation time, PTT or heparin.

49.- The multiple test cartridge of claim 46, wherein the test site measures the protrusion time (TP).

50.- A method of turning blood samples into an automated sample collection system that has a fluid access path other than a drug adapted to be connected to a fluid source other than a drug, a patient access route adapted to deliver fluid other than a drug to the patient and, alternatively, draw blood from the patient, the access route to the fluid other than a drug and the access route to the patient being connected through a fluid path, a first valve that It works to selectively isolate the patient from the fluid path, and a sample pathway selectively connectable to the fluid path through a second valve, the steps comprising: 1. Filling the fluid pathway to the patient with fluid other than a drug; 2. Extract the fluid other than a drug from the patient in order to draw the patient's blood in the fluid path, to a point beyond the sample pathway; 3. Isolate the patient from the sample path by closing the first valve; 4. Open the second valve to allow blood to enter the sample path; and 5. Move the blood through the sample path to the analyzer.

51.- The method of claim 50, wherein the blood moves through the sample path to the analyzer through the step of flowing fluid other than a drug through the access path to the fluid other than? drug in the fluid pathway.

52. The method of claim 50, wherein the blood is moved through the sample path to the analyzer by passing blood from the sample path to the analyzer.

53. The method of claim 50, wherein in step 2? N detector generates a signal indicating that the blood has moved in the fluid path to a point beyond the sample path.

54. The method of claim 50, wherein the signal generated by the detector is used to cause the termination of the patient's blood draw through the fluid path.